"Medicine is a social science, and politics is nothing else but medicine on a large scale"—Rudolf Virchow

December 09, 2016

Ancient rashes that scar the faces of Egyptian mummies have long been cited as evidence that smallpox ravaged the region more than 3000 years ago. But now, a study of viral DNA extracted from a 17th century child mummy—the oldest known sample of any virus—suggests that the deadliest form of smallpox emerged in humans much more recently, just in time to hitchhike with New World explorers and decimate populations around the world.

If the team’s analysis is right, it would “challenge many of the current beliefs about one of the most notorious pathogens in human history,” says historian Kyle Harper of the University of Oklahoma in Norman, who was not involved with the work.

The team behind the new study recovered the smallpox virus by accident. Researchers in Lithuania and Finland hoping to gather DNA from a more obscure virus collected tissue from the mummified remains of a young child found within the mid-17th century crypt of the Dominican Church of the Holy Spirit of Vilnius.

The child had no visible pox marks, but when the researchers sent the sample to the ancient DNA lab of Hendrik Poinar at McMaster University in Hamilton, Canada, his postdoc Ana Duggan got a big surprise. The sample was rich with variola, the virus that causes smallpox, the team reports today in Current Biology.

The large quantity of the virus allowed the researchers to construct a high-quality copy of its genome, the first from such an old virus. (The most ancient pathogens sequenced have been from bacterial DNA, including one that caused the plague 1600 years ago.)

The team was also surprised to find that the child mummy’s ancient viral DNA shared many distinct features with modern strains of the variola virus, including several mutations, suggesting they were closely related. The researchers built a family tree of 49 modern strains and the child’s ancient one, and traced the evolution of all of them back to a common ancestor that arose between 1530 and 1654 C.E.

This date is remarkably recent—only a hundred years or so before the time of the child mummy, and long after the dynasties of Egyptian pharaohs. It’s also much later than other accounts of epidemics, such as pustulous rashes from fourth century China and the Antonine Plague in Rome in 165 C.E., which have been attributed to smallpox by historians. These people may have suffered from chickenpox or measles instead, says Poinar, or from a different type of less deadly pox, which has since gone extinct.

But where did this new, deadly strain of variola come from in the 16th and 17th centuries? One possibility is that it could have lurked in an animal host and jumped to humans. Alternately, a mutation may have arisen in variola in humans that made it more deadly. If it did come from animals, it could still persist there, with the potential of reinfecting humans again, Poinar says.

The question that springs to mind is what disease the Spanish were carrying when they invaded Mexico in 1520, ten years before the earliest emergence of smallpox. The Conquest was vastly aided by European diseases like measles, and smallpox is generally assumed to have been the chief killer.

August 21, 2016

There are few people in the field of global public health so well-known that you merely need to utter two initials to evoke instant recognition.

But to raise in conversation Dr. Donald Ainslee Henderson, the man who led the successful effort to eradicate smallpox, all anyone ever bothered to say was “D.A.”

Henderson, a few weeks shy of his 88th birthday, died late Friday of complications that arose after he recently fractured a hip.

Towering in physical stature as well as in reputation, Henderson had a booming voice, which he used to great effect. He did not hesitate to express his views — even if they were not shared by others.

“D.A. was a giant intellectually, he was a giant in his personality, and he didn’t shy away from controversy,” said his friend Michael Osterholm, director of the University of Minnesota’s Center for Infectious Diseases Research and Policy.

Dr. Bill Foege, a friend and colleague for over 50 years, agreed.

“He was a person of strong convictions,” said Foege, who served as director of the Centers for Disease Control and Prevention from 1977 to 1983 and who first met Henderson at the CDC in 1962.

“I always think that was one of the attributes that provided for leadership because people don’t like to follow someone who’s uncertain about where they’re going. He brought a certain certainty to everything he did.”

Before taking the lead in the smallpox eradication program, Henderson was the CDC’s director of disease surveillance. His mentor had been Alexander Langmuir, the epidemiologist who founded the CDC’s renowned program to train disease detectives.

“I remember with Alex once talking about a subject and he presented his side and I said: ‘But it’s worth looking at the other side,’” Foege recalled. “And he slammed his fist down on his desk and said ‘There is no other side.’”

“D.A. got part of his training in this environment of absolute certainty.”

Henderson also shared Langmuir’s core belief that good surveillance is crucial to disease control.

“He always stressed the fact that without comprehensive disease surveillance, you just couldn’t run an effective public health program,” said Osterholm.

Tapped to lead the smallpox eradication program in 1966, Henderson moved to the World Health Organization, working as chief medical officer for the program.

In 1977 the world saw its last case of wild smallpox infection — a few cases infected through lab accidents happened later — and the disease was declared eradicated in 1980. To this day smallpox remains the only human disease ever eradicated.

August 20, 2016

Donald Ainslie Henderson, a former dean of Johns Hopkins Bloomberg School of Public Health who led the campaign to eradicate small pox, died in Baltimore on Friday.

Henderson, who was known as D.A., died following complications from a hip fracture at the age of 89 the UPMC Center for Health Security reported.

"D.A. Henderson truly changed the world for the better," Director of the UPMC Center for Health Security Tom Inglesby said. "He led the effort to rid the world of smallpox. He advised presidents. He was honored by countries around the planet. He changed the way schools of public health teach the next generation. With all of that, he still took the time to be a mentor to countless young people, and was a great friend. He is truly irreplaceable, and I will miss him."

Henderson was born on Sept. 7, 1928 in Lakewood, Ohio to David Alexander Henderson, an engineer with Union Carbide, and Grace Eleanor Henderson, a nurse.

He graduated from Oberlin College, from University of Rochester School of Medicine and Johns Hopkins School of Hygiene and Public Health in 1960 and served as a medical resident at the Mary Imogene Bassett Hospital in Cooperstown, New York.

From 1966 to 1977 he served as Director of the World Health Organization's global smallpox eradication campaign where he and his team became the only group to ever successfully eradicate a human disease.

Currently 24 people are in hospital in Salekhard, on the Arctic Circle, after contracting potentially lethal anthrax from unfrozen reindeer or human burial sites, but scientists say this is far from the only threat as climate change grips Siberia.

Anthrax spores are already 'on the loose' on the Yamal peninsula, according to one scientist, and this should act as a warning of the real risk of a return of eradicated smallpox from melting permafrost which allows the erosion of river banks at sites where victims were buried, said another.

'Back in the 1890s, there occurred a major epidemic of smallpox,' said Boris Kershengolts, deputy director for research at the Institute for Biological Problems of Cryolithozone, of the Siberian Branch of the Academy of Sciences.

'There was a town where up to 40% of the population died. Naturally, the bodies were buried under the upper layer of permafrost soil, on the bank of the Kolyma River. Now, a little more than 100 years later, Kolyma's floodwaters have started eroding the banks.'

Experts from the Novosibirsk-based Virology and Biotechnology Centre had conducted research in the area, said Sergey Netesov, chief of the bionanotechnology, microbiology and virology laboratory at the natural sciences department of Novosibirsk State University.

The corpses they studied bore sores that looked like those smallpox might cause, he told an intriguing and troubling TASS video conference involving multi-disciplinary experts on the implications of the outbreak of anthrax on the Yamal peninsula in northern Siberia.

While the virus itself was not found, some fragments of its DNA were noted. 'This type of research should go on,' he urged. 'Examining deeper burials might help clear up the situation.'

Yamal and the anthrax outbreak now underway - the first for 75 years - should act as a warning, he said, calling for a more serious attitude to preventive measures against dangerous infections.

While the number of people hospitalised with anthrax has halved since Friday, two dozen people remain infected by the disease which also killed more than 2,300 reindeer.

'The Yamal outbreak is a reason enough to finance research into the diagnostics and prevention of exceptionally dangerous infections,' he said.

He explained there are there are thousands of such cattle graves across Russia and many of them are inside the Arctic Circle, which last month - July - experienced the warmest temperatures on record rising to 35C.

May 25, 2016

Via The New York Review of Books, Dr. Annie Sparrow reviews Sonia Shah's Pandemic: Tracking Contagions from Cholera to Ebola and Beyond: The Awful Diseases on the Way by Annie Sparrow. It's a wonderful review by a knowledgeable writer. Excerpt:

Shah’s thesis is that pandemics are the product of complex human behavior. In her view, development, urbanization, and population growth transform harmless animal microbes into human pathogens. Empire-building takes humans into animal habitats, while climate change caused by human activity and deforestation forces animals into urban areas; industrial poultry, cattle, and pig farms also bring humans into greater contact with animals.

The “cholera paradigm” is a term coined by the microbiologist Rita Colwell. It means that the environment—biological, social, political, and economic—is both the source and driver of today’s emerging diseases in ways resembling the spread of cholera.

And as long as we're on the subject, here's my Tyee review of the book—equally positive, but not as well informed as Dr. Sparrow's.

May 14, 2015

Saudi Arabia's Ministry of Health (MOH), which reported 9 MERS-CoV cases on May 11, has added 3 more in the past 3 days and reported 2 deaths in previously reported cases as it is apparently grappling with a Web site failure, switching to a new—and detail-limited—reporting system, or both.

On May 12 the agency reported one new case of MERS-CoV (Middle East respiratory syndrome coronavirus) in Riyadh. But it provided only an outbreak map in Arabic on a new site (http://www.wecanstopthis.com/en), while its traditional reporting site has remained inactive since May 11.

The MOH also provided no table with details, as has been its custom, so no further information is available about the May 12 case. The new site also provides no access to archived daily MERS-CoV reports. The agency made no announcement of the changes.

Yesterday the MOH confirmed two more cases, this time with details. The first patient is a 49-year-old man who is hospitalized in a ward in Riyadh. He is not a health worker and reported no exposure history.

The second patient is a 61-year-old man hospitalized in an intensive care unit in Hofuf. He had both exposure to camels and indirect exposure to camels, possibly through another person. He is not a household contact of a confirmed case-patient, however, and had no exposure in a healthcare setting. He also is not a health worker.

On May 11 the MOH reported four MERS cases in Hofuf that may be part of a family cluster. Yesterday's patient is not part of that cluster, since he had no contact with a household member with MERS-CoV.

Today the MOH reported the MERS-related death of a patient in Riyadh without divulging further information. It listed the country's MERS-CoV total as 999 cases, 433 deaths, and 14 patients still undergoing treatment.

In connection with the MERS page, my spies tell me the pause is temporary while they overhaul the site. I'll believe it when I see it.

July 16, 2014

Government inspectors have been warning for years that labs used to handle dangerous agents such as anthrax have been poorly regulated and that the lack of oversight has put the public at risk, yet little has been done to heed their warnings, an official said Wednesday.

And no one’s listened to repeated calls for research to be done so that a cohesive national policy can help agencies do a better job of keeping lab workers and the public safe, a Government Accountability Office expert testified.

Yet Centers for Disease Control and Prevention director Dr. Tom Frieden said several startling incidents involving anthrax, smallpox and other dangerous pathogens came as a “wake-up call” to his agency.

The House Energy and Commerce health subcommittee opened a hearing Wednesday into the lapses, in which CDC workers were exposed to potential live anthrax bacteria, a USDA lab was sent a batch of avian influenza virus contaminated with highly pathogenic H5N1 bird flu, and a boxfull of glass vials full of live smallpox virus was discovered squirreled away in a lab on the National Institutes of Health campus.

CDC says it's cracking down, but the GAO says the agency should not have been surprised.

“GAO’s past work has found a continued lack of national standards for designing, constructing, commissioning, and operating high-containment laboratories,” the GAO’s Nancy Kingsbury told the hearing in written, prepared testimony. “This deficiency may be more critical today than five years ago when we first reported on this concern.”

There had to be a sinking feeling in the chest of every researcher who works in a high-containment research laboratory last Friday when the U.S. Centers for Disease Control and Prevention (CDC) released its report on three worrisome incidents that raised safety questions at two well-respected government facilities. But it is likely the sensation was most acute for the influenza scientists who work in a controversial field known as gain-of-function research.

On Friday Director Tom Frieden revealed that someone in the CDC's influenza division had accidentally contaminated a vial of a relatively mild bird flu virus with the worst one known, H5N1. The Atlanta-based CDC then shipped the vial to unsuspecting researchers at the U.S. Department of Agriculture’s Southeast Poultry Research Laboratory up the road in Athens, Ga., who used its contents to infect some unlucky chickens.

There is no suggestion the unfortunate event was anything other than human error, and no one—except the chickens—was made ill as a result of the mistake. But the fact that it happened, and could happen again, has given valuable ammunition to a group of scientists who have been arguing for the past couple of years that gain-of-function work on influenza viruses is too dangerous to undertake.

Such studies take flu viruses found in nature and, in essence, try to make them more dangerous. The aim is to see what it would take for viruses like H5N1, which currently rarely infect people, to gain the ability to easily transmit to and among us. Coughs and sneezes propel human flu viruses through populations, and scientists have found that by adding mutations and passing viruses from ferret to ferret enough times, they can push bird viruses to spread that way among the animals, which often stand in for people in flu research.

The stated scientific aim for such experiments is to speed up the detection of naturally occurring viruses that might acquire these more dangerous skills in the wild. But the end result is the formation of nasty pathogens with the potential to trigger disastrous flu pandemics if they were ever to escape the confines of the labs. After all, in its wild form H5N1 kills about 60 percent of the people it infects.

Ron Fouchier, a Dutch virologist who is one of the biggest names in gain-of-function research, believes the CDC accident is going to make life more difficult for all those working on dangerous pathogens, not just those in the gain-of-function field. “When incidents like this happen, it’s going to be bad for all of us,” says Fouchier, who is based at the Erasmus Medical Center in Rotterdam.

These studies are done in so-called biosafety level (BSL) 3-enhanced labs, which have layers of safeguards in place to keep unauthorized people out and pathogens in as well as to ensure lab workers do not become infected in the course of their work. These precautions are there to protect the lab workers, obviously.

But they are also there to protect the public by making sure that the researchers and technicians do not serve as unwitting carriers who wind up spreading these germs once they leave the lab. Indeed, the Erasmus scientists who work with Fouchier on H5N1 gain-of-function work are among a very few people on Earth to have been vaccinated against the bird flu virus, although that is not true of all flu scientists doing this type of research.

Fouchier insists this work should be done and can be done safely. “I would really doubt that these things would happen in my laboratory,” he says of the CDC incident. “But of course I understand that the director of CDC would have said the same thing.”

Still, he knows critics of the field will hold up this incident as proof that even the best of laboratories are subject to human error, because the CDC flu lab is considered among the best in the world.

July 14, 2014

On the heels of several mishaps involving deadly pathogens, U.S. officials are reconvening an expert advisory panel that hasn’t met in nearly 2 years. But the government has also dismissed 11 of the original members of the 23-person panel, called the National Science Advisory Board for Biosecurity (NSABB).

“We had no inkling it was going to happen this way,” says Paul Keim, a pathogen genomics researcher at Northern Arizona University in Flagstaff who formerly chaired NSABB and has been on the panel since it was formed in 2005.

The 11 members learned they were being dismissed Sunday evening in an e-mail from the board’s executive director, Mary Groesch, who works at the U.S. National Institutes of Health (NIH), NSABB’s overseer.

The e-mail prompted this tweet from NSABB member Michael Imperiale of the University of Michigan, Ann Arbor: “#NIH just gave remaining inaugural NSABB members pink sheets. Bizarre time to eliminate all institutional memory.”

The e-mail, which ScienceInsider obtained, cheerily informs Imperiale, Keim, and the other original NSABB members that the board will be reconvening in the fall without them. “I wanted to tell you that a new slate of NSABB members has been approved as your replacements, and thus your service on the board is ending,” Groesch wrote. “Since you have all been so gracious as to extend your service for several years beyond your initial term, this may come as welcome news!”

NSABB advises and guides the U.S. government about “dual use” research that involves biological agents that could be used as bioweapons. In 2011, it became embroiled in heated debates about “gain-of-function” experiments with the deadly avian influenza virus H5N1 that made it more transmissible in mammals. Last week, Tom Frieden, director of the U.S. Centers for Disease Control and Prevention, held an unusual press conference to discuss three separate, recent mistakes involving lab safety with smallpox, influenza, and anthrax. He said such breaches “should never happen.”

Original board member Michael Osterholm, director of the Center for Infection Disease Research and Policy at the University of Minnesota, Twin Cities, said he had expected to serve until sometime in 2015.

“I don't know why they do or don’t do things at the NSABB,” Osterholm told ScienceInsider. “I gave up some time ago trying to predict that.” The board has 12 other members who apparently are continuing.

July 12, 2014

Based on an internal review called for by the CDC Director, the report released today concludes that the scientists’ failure to follow an approved, written study plan that met all laboratory safety requirements led to dozens of employees being potentially exposed.

The report also found that there was a lack of standard operating procedures to document when biological agents are properly inactivated in laboratories as well as a lack of adequate laboratory oversight of scientists performing work in these labs.

The report concludes that the critical nature of CDC investigations to detect and respond to naturally occurring and man-made events with select agents while ensuring the safety of staff are paramount and should be guided by the highest standards.

In response to these incidents, CDC has initiated following steps, in addition to the moratorium:

• Established a high-level working group, reporting to the CDC Director, to, among other duties, accelerate improvements in laboratory safety, review and approve, on a laboratory-by-laboratory basis, resumed transfer of biological materials outside of BSL3 and BSL4 laboratories, and serve as the transition group for the single point of accountability on laboratory safety called for in the review of the potential exposure to anthrax incident.

• Begun the process of establishing an external advisory group for laboratory safety. Invitations to participate in this group will be issued by July 18, 2014.

• Initiated an investigation to determine root causes that led to contamination of another avian influenza virus by the H5N1 virus.

• Reported the incident through the proper channels to the select agent oversight body, APHIS.

• Established a review group, under the direction of CDC’s Associate Director for Science, to look at the systems, procedures, and personnel issues leading to this event and means of preventing similar events in the future. This review will be done in conjunction with the internal investigation and in coordination with the working group.

• Undertaking appropriate personnel action expeditiously.

CDC has also implemented or is in the process of implementing the following key recommendations highlighted in the report to address the root causes of the anthrax incident:

• CDC will establish a CDC-wide single point of accountability for laboratory safety.

• The Bioterrorism Rapid Response and Technology (BRRAT) Laboratory will not be conducting work with any select agent until a series of reviews and approvals are completed. BRRAT laboratory scientists do not have access to select agents, which have been placed in storage-only mode. These restrictions will remain in place until changes have been put in place to prevent similar future incidents.

• Appropriate personnel action will be taken with respect to individuals who contributed to or were in a position to prevent this incident.

• All inactivation procedures for laboratories working with select agents and other dangerous pathogens throughout CDC are being carefully reviewed and will be updated as needed.

• CDC will improve its response to future internal incidents by the rapid establishment of an incident command structure, as CDC uses for external events.

• The implications for the use of select agents, including for CDC’s regulatory functions through CDC’s Division of Select Agents and Toxins will be carefully reviewed to incorporate any lessons learned.

The incident amounts to an "own goal" miraculously prevented by the goalie's heroic lunge. If you watch soccer (such as the almost-over World Cup), you've seen furious goalies reaming out their defenders for the lapses that permitted such disasters.

Health ministries and agencies around the world should be taking copious notes about the way CDC Director Dr. Tom Frieden has handled this. Any health bureaucrat can rattle on about "transparency" and "accountability," but Frieden is actually doing it. The CDC is practically the Supreme Court of epidemiology, and this incident could seriously tarnish its reputation.

Instead, Frieden has revealed the problem in detail. He's also revealed his feelings about it, completely ditching the bland "Father knows best" attitude so beloved of health ministers with bad outbreaks to explain.

He hasn't completely lost his political cool, however. "Undertaking appropriate personnel action expeditiously" sounds like a euphemism for heads rolling in all directions sometime early next week. As they should be, if CDC is to maintain what goalies call a clean sheet.